Research in the Blacklow laboratory is centered around the molecular logic of normal and pathogenic Notch signaling. Activating mutations in human Notch1 are found in more than half of human T-cell leukemias, and a key goal of current research is therefore to develop new classes of selective Notch inhibitors.

Dysregulation of protein homeostasis drives many types of cancer, infection and neurodegeneration. The mission of our group is to develop first-in-class inhibitors and prototype drugs for deubiquitylating enzymes, a class of enzymes responsible for regulating proteostasis, that can be utilized to pharmacologically validate members of the gene family as new targets for cancer treatment and other diseases.

Our research focuses on deciphering the molecular mechanisms of metabolic disease, and using this information to develop targeted therapeutic strategies. We apply mass spectrometry, biochemical, and genetic approaches to identify mitochondrial metabolic pathways that control protective and pathological cascades initiated by this organelle.

The Cohen Lab develops physical tools to study molecules and cells. They work on imaging voltage in brains, hearts, embryos, and microorganisms; we study DNC mechanics; they study the effects of weak magnetic fields on chemical reactions; and they study the fundamental physics of light-matter interactions.

Our research involves the chemical biology of protein post-translational modifcations (PTMs) in the context of signaling, epigenetics, and cancer. We develop and apply chemical approaches including protein semisynthesis and small molecule probes to the study of protein phosphorylation, acetylation, ubiquitination and other PTMs in enzymes and cellular networks.

We combine structural biology, cell biology and biochemical reconstitutions to address the mechanistic principles that govern signaling through the ubiquitin proteasome system. We seek to leverage our molecular understanding to propose and test new avenues of therapeutic intervention.

Our goals are to understand the molecular interactions controlling protein and lipid mobility and distribution in cell membranes, the roles these mechanisms play in interactions between cells, and the relationships between derangements in these mechanism and the pathophysiology of disease.

Our group seeks to define and understand the mechanisms leading to tumorigenesis. We focus on elucidating the protein kinases responsible for specific cancers and developing small molecule inhibitors of these kinases as tools for discovery and as potential therapeutics.

ChemicaChemical neurobiology of neuropsychiatric disorders: We use chemical biology along with molecular and cell biology approaches to understand how the nervous system functions in health and disease. We are particularly interesteinterested in the molecular mechanisms of neuroplasticity and how these are affected in psychiatric and neurodegenerative disorders and may be targeted therapeutically.

Dr. Hung is working at the interface of chemical biology, infectious disease, and genetic/genomics to better understand the host-bacterial pathogen interaction and explore new paradigms for how to intervene on infection therapeutically. She has been developing and exploring models to identify molecules that disrupt the pathogen-host interaction or alter bacterial behavior under conditions used to model in vivo infection.

The central focus of our laboratory is to understand BAF complex pathway-of-assembly, to determine the complex subunit and associated protein factor composition of oncogenic BAF complexes, and to define the mechanistic basis of locus-specific and genome-wide retargeting.

Our central goal is to develop novel chemical biology and functional genomic approaches to illuminate molecular mechanisms in epigenetics and gene regulation, while exploring the promise of chromatin regulators as therapeutic targets for cancer.

David R. Liu is Professor of Chemistry and Chemical Biology at Harvard University, Howard Hughes Medical Institute Investigator, and Vice-Chair of the Faculty of the Broad Institute. His research integrates chemistry and evolution to illuminate biology and enable novel therapeutics through the development and application of powerful technologies, including DNA-templated synthesis (DTS), phage-assisted continuous evolution (PACE), and base editing, a genome editing method that converts a specified base pair to a different base pair in living cells without cutting DNA. He has also founded several therapeutics companies.

The Mootha lab aims to characterize the structure and dynamic properties of the biological networks underlying mitochondrial function, link variation in these parameters to genetic variation, and exploit the network properties of the organelle to design therapies for human disease.

Our research focuses on exploring novel therapeutic strategies for cancer through a multi-disciplinary approach, including synthetic chemistry, medicinal chemistry, chemical biology, computational biology, and biology. We study gene regulatory pathways including epigenetic proteins, chromatin modification enzymes, and transcription factors. We seek understanding of the biological relevance of these targets in cancer, as well as develop novel therapeutic strategy.

The Hedgehog signaling pathway has critical roles in the embryonic development, in maintaining stem cells and in human cancer. We use biochemistry, cell and chemical biology to understand how vertebrate cells send and interpret Hedgehog signals. We also develop new chemical tools within the area of cell-cell signaling and cell cycle.

By examining a series of alleles linked to a disease, we can learn the effect of modulating candidate therapeutic targets in terms of both efficacy and safety. This approach to therapeutic discovery requires that we innovate chemical biology; for example, by discovering small molecules that impart on a therapeutic target the biochemical mechanism of disease protection seen with protective alleles.

The Silver Lab works at the interface between systems and synthetic biology to design and build biological systems in both mammalian and prokaryotic cells. Some current projects include analysis of cells that remember past events, cell-based computation and therapeutics, and metabolic engineering for bio-energy and sustainability.

Professor of Biological Chemistry and Molecular Pharmacology; Professor of Pediatrics

The Wu laboratory of structural immunology focuses on elucidating the molecular mechanism of signal transduction by immune receptors, especially innate immune receptors. We are especially interested in the formation of supramolecular signaling complexes (“signalosomes”) upon receptor activation and their implications in cell signaling properties.

The Wu laboratory is interested in using chemical biology and functional genomics approaches to study lipid biology, developmental signaling networks and cellular processes in normal physiology and diseases.

My group utilizes chemical tools to study the interaction of viral pathogens with the host cell. We are especially interested in using chemical tools to elucidate molecular mechanisms underlying the replication of viral pathogens to pioneer and validate new antiviral targets and strategies.